Clofarabine, Cytarabine, and Idarubicin in Treating Patients With Intermediate-Risk or High-Risk Acute Myeloid Leukemia or High-Risk Myelodysplasia (AML-14A)
Recruitment status was: Recruiting
RATIONALE: Drugs used in chemotherapy, such as clofarabine, cytarabine, and idarubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.
PURPOSE: This randomized phase I/II trial is studying the side effects and best dose of clofarabine and to see how well it works when given together with cytarabine and idarubicin in treating patients with intermediate-risk or high-risk acute myeloid leukemia or high-risk myelodysplasia.
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Clofarabine in Combination With a Standard Remission Induction Regimen (AraC and Idarubicin) in Patients 18-60 Years Old With Previously Untreated Intermediate and Bad Risk Acute Myelogenous Leukemia (AML) or High Risk Myelodysplasia (MDS) : a Phase I-II Study of the EORTC-LG and GIMEMA (AML-14A Trial)|
- Toxicity as assessed by CTCAE v3.0 (Phase I)
- Response rate (Phase II)
- Toxicity as assessed by CTCAE v3.0 (Phase II)
- Response rate (Phase I)
- Duration of survival
- Duration of survival from complete remission (CR)/CR with incomplete hematopoietic recovery (CRi) rate
- Disease-free survival from CR/CRi
- Incidence of relapse and incidence of death in CR/CRi
|Study Start Date:||November 2008|
|Estimated Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
Experimental: Arm I
Patients receive idarubicin IV over 5 minutes on days 1, 3, and 5, cytarabine IV continuously on days 1-10, and clofarabine IV over 1 hour on days 2, 4, 6, 8, and 10.
Given IVDrug: cytarabine
Given IVDrug: idarubicin
Experimental: Arm II
Patients receive idarubicin IV and cytarabine IV as in arm I. Patients also receive clofarabine IV by push injection over 10 minutes on days 2, 4, 6, 8, and 10.
Given IVDrug: cytarabine
Given IVDrug: idarubicin
- To determine the optimum dose of clofarabine in combination with cytarabine and idarubicin in patients with previously untreated intermediate- and high-risk acute myeloid leukemia or high-risk myelodysplasia. (Phase I)
- To determine the safety and tolerance of this regimen in order to determine the recommended phase II dose. (Phase I)
- To explore the antitumor activity of this regimen in these patients. (Phase II)
- To determine the activity expressed as complete remission (CR)/CR with incomplete hematopoietic recovery (CRi) rate following induction therapy. (Phase II)
- To determine the activity expressed as CR/CRi rate following induction (1 or 2 courses) and consolidation therapy. (Phase I)
- To determine hematopoietic recovery (platelets and neutrophils) after induction and consolidation therapy.
- To determine safety and tolerability of this regimen. (Phase II)
- To determine activity expressed as CR/CRi rate after consolidation therapy. (Phase II)
- To determine feasibility of blood CD34 harvesting after consolidation therapy. (Phase II)
- To determine disease-free and overall survival from CR/CRi. (Phase II)
OUTLINE: This is a multicenter, phase I, dose-escalation study of clofarabine followed by an randomized phase II study. Patients are stratified according to center, and presence of poor prognostic features (WBC at diagnosis ≥ 100,000/μL vs presence of very high risk cytogenetic features -5/5q-, -7/7q-, presence of complex abnormalities [> 3 abnormalities], 3q, t[6;9], or t[9;22]). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive idarubicin IV over 5 minutes on days 1, 3, and 5, cytarabine IV continuously on days 1-10, and clofarabine IV over 1 hour on days 2, 4, 6, 8, and 10.
- Arm II: Patients receive idarubicin IV and cytarabine IV as in arm I. Patients also receive clofarabine IV by push injection over 10 minutes on days 2, 4, 6, 8, and 10.
- Consolidation therapy: Patients receive cytarabine IV over 2 hours every 12 hours on days 1-6 and idarubicin IV over 5 minutes once daily on days 4-6.
After completion of study therapy, patients are followed periodically for 12 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00838240
|Institut Jules Bordet|
|University Hospital Rebro|
|Hôpital Saint Antoine AP-HP|
|Azienda Ospedallera Universitaria - Policlinico Tor Vergata|
|Univesita Degli Studi "La Sapienza"|
|Leiden University Medical Center|
|Radboud University Nijmegen Medical Center|
|Jeroen Bosch Ziekenhuis|
|s' Hertogenbosch, Netherlands|
|Principal Investigator:||Roel Willemze||EORTC (Phase I) - Leiden University Medical Center, NL|
|Principal Investigator:||Dominik Selleslag||EORTC (Phase II) - AZ Sint-Jan, BE|
|Principal Investigator:||Giovanna Meloni||GIMEMA (Phase I & II) - Universita Degli Studi "La Sapienza", IT|